Standardized Input Function for 18F-FDG PET Studies in Mice: A Cautionary Study

The aim of this study was to assess the accuracy of a standardized arterial input function (SAIF) for positron emission tomography 18F-FDG studies in mice. In particular, we tested whether the same SAIF could be applied to populations of mice whose fasting conditions differed.

The SAIF was first created from a population of fasting mice (n = 11) and validated within this group using a correlation analysis and a leave-one-out procedure. Then, the SAIF was prospectively applied to a population of non-fasting mice (n = 16). The SAIFs were scaled using a single individual blood sample taken 25 min after injection. The metabolic rates of glucose (CMRglc) calculated with the SAIFs were compared with the reference values obtained by full arterial sampling (AIF).

In both populations of mice, CMRglc values showed a very small bias but an important variability. The SAIF/AIF CMRglc ratio in the fasting mice was 0.97 ± 0.22 (after excluding a major outlier). The SAIF/AIF CMRglc ratio in the non-fasting mice was 1.04 ± 0.22. This variability was due to the presence of cases in which the SAIF poorly estimated the shape of the input function based on full arterial sampling.

Although SAIF allows the estimation of the 18F-FDG mice input function with negligible bias and independently from the fasting state, errors in individual mice (as high as 30-50%) cause an important variability. Alternative techniques, such as image-derived input function, might be a better option for mice PET studies.